Hematopoiesis is maintained by a hierarchical system where hematopoietic stem cells (HSCs) give rise to multipotent progenitors, which in turn differentiate into all types of mature blood cells. Clonal stem-cell disorders in this system lead to Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPNs), Myelodysplastic Syndromes (MDS) and Myelodysplastic/Myeloproliferative disorders.
Among these disorders, myelodysplastic/myeloproliferative neoplasms include four myeloid diseases grouped in 1999 by the WHO: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), atypical chronic myeloid leukemia (aCML) and unclassified myelodysplastic/myeloproliferative syndromes (U-MDS/MPS) (Vardiman et al., Blood 114:937-951, 2009).
CMML is a rare disorder with an estimated incidence of 1 case per 100 000 persons per year. Median age at presentation is 70 years, and presenting manifestations may include those of bone marrow failure and systemic symptoms. Hepatomegaly and splenomegaly are found in some patients, and the white blood cell count is typically increased.
The current diagnosis of CMML relies on the criteria defined by WHO in 2008 (Vardiman et al., Blood 114:937-951, 2009). CMML definition is based on only one positive criterion, which is the elevation of monocytes to more than 1×109/L, measured over at least 3 months. Negative criteria exclude i) acute leukemia by cytological examination of the blood and bone marrow showing a percentage of blast cells lower than 20%, ii) chronic myeloid leukemia by demonstrating the lack of BCR-ABL fusion gene, and iii) the so-called Myeloid and Lymphoid Neoplasms with Eosinophilia (MLN-Eo) when eosinophilia is combined with monocytosis by checking the lack of gene rearrangement involving a PDGFR (Platelet-Derived Growth Factor Receptor) or FGFR (Fibroblast Growth Factor Receptor) gene.
However, some patients with myelofibrosis (MF) in proliferative phase and some patients with chronic inflammatory disease or late stage metastatic solid tumor and reactive monocytosis, meet this criteria, whereas patients with dysplastic CMML and low white blood cell (WBC) count and so less than 1×109/L of monocytes, do not. The differentiation with unclassified MDS/MPN can thus be problematic. Genetic analyses failed to identify a specific cytogenetic or genetic abnormality in CMML, although a characteristic molecular fingerprint based on the high frequency of mutations in TET2, SRSF2 and ASXL1 genes, has been established.
Additional efforts are needed to improve the disease definition and facilitate its rapid and accurate identification in daily clinical practice. Thus there is still a need for a new diagnosis method of CMML which is rapid, efficient and simple.